童雨田,王懷新※(綜述),胡奉環(huán)(審校)
(1.濰坊醫(yī)學(xué)院附屬益都中心醫(yī)院心內(nèi)科,山東 濰坊 262500; 2.阜外心血管病醫(yī)院心內(nèi)科,北京 100037)
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血栓抽吸在急性心肌梗死急診介入治療時(shí)的應(yīng)用進(jìn)展
童雨田1,王懷新1※(綜述),胡奉環(huán)2(審校)
(1.濰坊醫(yī)學(xué)院附屬益都中心醫(yī)院心內(nèi)科,山東 濰坊 262500; 2.阜外心血管病醫(yī)院心內(nèi)科,北京 100037)
摘要:急性心肌梗死急診心臟介入治療時(shí)發(fā)生的無(wú)復(fù)流或慢血流可影響治療效果和臨床預(yù)后,其中主要的機(jī)制是血栓栓塞。從理論上講血栓抽吸應(yīng)是有效的處理措施。近年來(lái)大量的臨床試驗(yàn)證實(shí)血栓抽吸不僅可有效地使梗死相關(guān)動(dòng)脈再通,并使冠狀動(dòng)脈微循環(huán)保持通暢,降低無(wú)復(fù)流和慢血流的發(fā)生率。最近臨床研究表明血栓抽吸可減輕病變心肌的炎癥反應(yīng),改善微循環(huán)功能,聯(lián)合溶栓抗栓藥物可減少血栓負(fù)荷,改善冠狀動(dòng)脈的血流灌注,減少梗死面積,抑制心室重塑,改善心功能,降低近期和遠(yuǎn)期主要不良心臟事件的發(fā)生率,降低晚期支架再狹窄的發(fā)生率并減少出血并發(fā)癥,從而改善預(yù)后。
關(guān)鍵詞:急性心肌梗死;血栓抽吸;主要不良心臟事件;經(jīng)皮冠狀動(dòng)脈介入
急性ST段抬高型心肌梗死(ST-segment elevated myocardial infarction,STEMI)的主要發(fā)病機(jī)制是斑塊破裂繼之血栓形成阻塞冠狀動(dòng)脈導(dǎo)致心肌缺血壞死[1],因此血栓抽吸(thrombus aspiration,TA)在理論上應(yīng)是開(kāi)通梗死相關(guān)動(dòng)脈的有效措施。自Beran等[2]應(yīng)用抽吸導(dǎo)管抽吸血栓治療STEMI以來(lái),由于技術(shù)和經(jīng)驗(yàn)方面的問(wèn)題得到的臨床結(jié)果不盡相同[3-4]。然而,近年來(lái)隨著抽吸導(dǎo)管的改進(jìn),抽吸技術(shù)的不斷完善,臨床研究規(guī)模加大,在臨床研究方面取得了較大進(jìn)展?,F(xiàn)就TA技術(shù)在急診經(jīng)皮冠狀動(dòng)脈介入(primary percutaneous coronary intervention,PPCI)治療中的應(yīng)用進(jìn)展綜述如下。
1TA技術(shù)加PPCI改善STEMI患者的心肌灌注
普遍認(rèn)為STEMI的最佳治療是盡早實(shí)施急診PPCI開(kāi)通梗死相關(guān)動(dòng)脈,最大限度地恢復(fù)心肌再灌注。常規(guī)的PPCI術(shù)可使梗死相關(guān)動(dòng)脈開(kāi)通,雖然90%的患者最終可獲得心肌梗死溶栓(thrombolysis in myocardial infarction,TIMI)血流分級(jí)3級(jí)血流,但這些患者中僅有2/3獲得心肌灌注血流分級(jí)(myocardial blush grade,MBG)2~3級(jí)血流[5],即獲得TIMI 3級(jí)血流者,仍有部分患者梗死心肌得不到正常的血供而影響預(yù)后。其主要原因被認(rèn)為是冠狀動(dòng)脈遠(yuǎn)端血栓栓塞、動(dòng)脈斑塊碎片栓塞、微循環(huán)水腫等引起冠狀動(dòng)脈微循環(huán)功能不全導(dǎo)致的冠狀動(dòng)脈無(wú)復(fù)流及慢血流[6]。因此,TA技術(shù)的產(chǎn)生和發(fā)展使STEMI的救治水平進(jìn)一步提高[7]。Amin等[8]對(duì)23個(gè)(5728例)隨機(jī)對(duì)照臨床試驗(yàn)的資料進(jìn)行薈萃分析,均為TA和遠(yuǎn)端血栓防護(hù)的PPCI,取栓方法包括手動(dòng)抽吸、真空抽吸、機(jī)械切除等,結(jié)果顯示血栓抽吸組患者M(jìn)BG 3級(jí)血流、TIMI 3級(jí)血流獲得率明顯提高,ST段回落速度和程度大于傳統(tǒng)PPCI組患者,這一大樣本的臨床研究初步展示了TA帶來(lái)的益處。最近Schleder等[9]薈萃分析了17個(gè)隨機(jī)對(duì)照TA、機(jī)械血栓切除后PPCI與常規(guī)PPCI的臨床試驗(yàn)(3909例),采用隨機(jī)效應(yīng)和固定效應(yīng)兩種模型進(jìn)行分析,發(fā)現(xiàn)血栓抽吸組患者TIMI 3 級(jí)血流的獲得率為88.5%,常規(guī)PPCI組為84.8%(OR=1.41,P=0.007),TA組患者M(jìn)BG 3 級(jí)血流的獲得率為47.8%,而常規(guī)PPCI組為32.1%(OR=2.42,P<0.001),TA組患者與常規(guī)PPCI組ST段回落的程度更為顯著(OR=2.30,P<0.001),手動(dòng)抽栓組30 d病死率與常規(guī)PPCI組比較降低了41%(P=0.005),但是機(jī)械血栓切除組病死率高于常規(guī)PPCI組(OR=2.07,P=0.07)。Kumbhani等[10]薈萃分析了18個(gè)TA和7個(gè)機(jī)械血栓切除的隨機(jī)對(duì)照臨床試驗(yàn)(5534例)的結(jié)果顯示,TA組ST 段在60 min內(nèi)回落,ST段回落更為顯著(RR=1.31,P<0.0001), MBG 3級(jí)獲得率顯著提高(RR=1.37,P<0.0001)。Waldo等[11]研究發(fā)現(xiàn),血栓抽吸后行PPCI比傳統(tǒng)的PPCI可獲得更高的TIMI 3級(jí)血流 (P<0.003),且提高了手術(shù)成功率(96%比83%,P<0.001),降低了術(shù)后需要血流動(dòng)力學(xué)支持的發(fā)生率,但不降低長(zhǎng)期病死率和主要不良心臟事件(major adverse cardiac events,MACE)的發(fā)生率。Costopoulos等[12]進(jìn)行了一項(xiàng)Meta分析將取栓分為手動(dòng)和非手動(dòng)取栓兩組,結(jié)果表明手動(dòng)抽吸血栓組ST段回落>70%的發(fā)生率顯著提高(P<0.0001),TIMI 3級(jí)血流的獲得率增高(P=0.01) ,MBG 3級(jí)血流獲得率增高(P<0.0001)。De Carlo等[13]研究發(fā)現(xiàn),血栓抽吸在改善心肌灌注的同時(shí)明顯降低了遠(yuǎn)端小動(dòng)脈栓塞的發(fā)生率(11.4% 比26.7%,P=0.02)。Chopard等[14]采用對(duì)比劑增強(qiáng)磁共振成像觀察血栓抽吸對(duì)微循環(huán)栓塞的影響,評(píng)估急性期和6個(gè)月的臨床結(jié)果。TA組急性早期微循環(huán)栓塞發(fā)生率低于對(duì)照組[(3.8±1.1)%比(7.6±2.1)%,P=0.003]; 晚微循環(huán)栓塞發(fā)生率也低于對(duì)照組[(2.1±0.9)% 比 (5.4±2.9)%,P=0.006],TA組梗死面積低于對(duì)照組, 6個(gè)月后TA組患者心肌梗死面積進(jìn)一步縮小,提示TA組患者有更多的心肌存活并回復(fù)。多因素回歸分析校正其他因素后,TA是梗死面積的獨(dú)立預(yù)測(cè)指標(biāo) (OR=0.34,95%CI0.03~0.71,P=0.01)。因此,TA在減少微循環(huán)栓塞的同時(shí)也縮小了梗死面積。以上大量的臨床研究表明TA后減少了血栓負(fù)荷,降低了冠狀動(dòng)脈遠(yuǎn)端微循環(huán)的栓塞發(fā)生率,降低了無(wú)復(fù)流和慢血流的發(fā)生率,從而改善了心肌再灌注。
2TA技術(shù)加溶栓抗栓藥物的PPCI進(jìn)一步提高心肌灌注
近年來(lái)研究發(fā)現(xiàn),由于STEMI患者到達(dá)導(dǎo)管室后多數(shù)血栓負(fù)荷量較大,單純TA的臨床效果減低,理論上聯(lián)合溶栓抗栓藥物可進(jìn)一步降低血栓負(fù)荷改善心肌灌注。Greco等[15]研究發(fā)現(xiàn),在TA之前通過(guò)抽吸導(dǎo)管向病變部位注射尿激酶20萬(wàn)U 與0.9%NaCl注射液對(duì)照,發(fā)現(xiàn)注射尿激酶再行TA的PPCI患者TIMI 3級(jí)血流的獲得率更高(90%比 66%,P=0.008),TIMI血流幀數(shù)降低[(19±15) 比(25±17),P=0.033],冠狀動(dòng)脈血流速度加快,MBG 2~3級(jí)血流獲得率增高(68%比45%,P=0.028),ST段回落程度>70%的發(fā)生率明顯增加(82%比55%,P=0.006)。隨訪6 個(gè)月后的MACE發(fā)生率降低(6%比21%,P=0.044)。TA聯(lián)合溶栓治療使冠狀動(dòng)脈血流和心肌灌注增加的同時(shí)也改善了6個(gè)月的臨床預(yù)后。Brener等[16]研究了452例STEMI患者,分別采用支架置入前冠狀動(dòng)脈內(nèi)TA術(shù)及冠狀動(dòng)脈罪犯血管內(nèi)注射血小板糖蛋白Ⅱb/Ⅲa受體拮抗劑阿西單抗,接受TA及冠狀動(dòng)脈內(nèi)注射阿西單抗的患者TIMI3級(jí)血流獲得率最高(P<0.0001),心肌梗死面積減少(15.1%比17.9%,P=0.03),絕對(duì)心肌梗死質(zhì)量減少差異有統(tǒng)計(jì)學(xué)意義(18.7 g比24.0 g,P=0.03)。Shimada等[17]采用薈萃分析前瞻性隨機(jī)對(duì)照研究試驗(yàn)資料,發(fā)現(xiàn)冠狀動(dòng)脈內(nèi)注射阿西單抗與靜脈內(nèi)注射相比,前者可使病死率降低56%(OR=0.44,95% CI 0.20~0.95,P=0.04),冠狀動(dòng)脈內(nèi)注射阿西單抗聯(lián)合TA使MACE減少67%(OR=0.33,95%CI0.18~0.61,P=0.0004),尤其對(duì)血栓負(fù)荷較大和高?;颊攉@益更大。Ahmed等[18]采用TA加冠狀動(dòng)脈內(nèi)注射阿西單抗與單純冠狀動(dòng)脈內(nèi)注射阿西單抗進(jìn)行比較, 發(fā)現(xiàn)PPCI術(shù)后90 min內(nèi)ST段完全回落發(fā)生率在血栓抽吸組增高 (P=0.002),多元回歸分析顯示TA是ST段回落的獨(dú)立預(yù)測(cè)指標(biāo) (OR=9.4,95%CI2.6~33.5,P=0.001)。而遠(yuǎn)端栓塞的發(fā)生率在常規(guī) PCI 組明顯增高。心肌酶的峰值水平差異無(wú)統(tǒng)計(jì)學(xué)意義。隨訪12個(gè)月,血栓抽吸組患者全因病死率顯著降低(P=0.032)。國(guó)內(nèi)學(xué)者Yan等[19]采用TA聯(lián)合冠狀動(dòng)脈內(nèi)注射替羅非班與單純TA的PPCI比較,前者TIMI 3級(jí)血流獲得率可達(dá)97%以上(P=0.04),心肌酶峰值顯著降低(P=0.03),認(rèn)為TA加替羅非班注射后的PPCI改善心肌灌注,保存更多心肌和帶來(lái)更好的臨床結(jié)果。TA聯(lián)合冠狀動(dòng)脈內(nèi)注射溶栓藥物的效果缺乏大規(guī)模的臨床研究資料,其真正臨床價(jià)值尚需進(jìn)一步研究。TA聯(lián)合抗血小板藥物阿西單抗有較多的循證醫(yī)學(xué)證據(jù),可明顯提高心肌再灌注并改善臨床預(yù)后,冠狀動(dòng)脈內(nèi)注射效果最佳,但用藥時(shí)機(jī)及劑量尚無(wú)成熟經(jīng)驗(yàn)和共識(shí)。
3TA技術(shù)加PPCI可減輕炎癥反應(yīng),降低支架再狹窄率
研究發(fā)現(xiàn),炎癥反應(yīng)和氧化應(yīng)激是促使動(dòng)脈粥樣硬化斑塊破裂及其帶來(lái)心肌損傷的主要機(jī)制,也是晚期支架內(nèi)再狹窄的重要機(jī)制。血栓內(nèi)纖維蛋白可網(wǎng)絡(luò)大量紅細(xì)胞和炎性細(xì)胞形成,病理檢查發(fā)現(xiàn)TA抽出的血栓成分包括血小板、紅細(xì)胞、纖維蛋白和髓過(guò)氧化物酶抗體陽(yáng)性細(xì)胞等炎性細(xì)胞成分,通過(guò)有效地抽吸還可抽吸出血栓上游滯留的血液,滯留的血液中含有較多的有害介質(zhì)如氧自由基、乳酸等,因此成功地抽吸減輕了病變及其周圍的炎癥反應(yīng)[20]。Dominguez-Rodriguez等[21]研究發(fā)現(xiàn),TA聯(lián)合冠狀動(dòng)脈內(nèi)注射阿西單抗可使患者血液中重要的致炎物質(zhì)可溶性CD40配體水平明顯降低(P<0.001),他們認(rèn)為TA技術(shù)聯(lián)合冠狀動(dòng)脈內(nèi)注射阿西單抗具有強(qiáng)大的抗炎療效。Bulum等[22]研究了TA對(duì)支架再狹窄的影響,結(jié)果顯示成功手動(dòng)TA明顯提高了6個(gè)月后最小管腔直徑[(2.25±0.90) mm 比(1.63±0.76) mm,P=0.005],大大降低支架直徑狹窄百分比(28.81%比 45.03%,P=0.017),并大大降低晚期支架管腔丟失[(0.73±0.84) mm比 (1.18±0.79) mm,P=0.035]。Shehata[23]研究了伴有糖尿病的STEMI患者TA對(duì)PPCI后支架再狹窄的影響,結(jié)果顯示成功手動(dòng)TA可使晚期支架管腔丟失顯著減少[(0.17±0.35) mm比(0.60±0.42) mm,P<0.001],支架內(nèi)再狹窄率顯著降低(4.0%比16.6%,P<0.001)。Belkacemi等[24]研究了急診PPCI時(shí)普通球囊置入裸支架,藥物球囊加裸支架和TA加藥物支架,結(jié)果表明TA組晚期支架管腔丟失最少(0.21±0.32) mm,P<0.01),二元再狹窄率最低(4.7%,P=0.01)。眾多的臨床對(duì)照試驗(yàn)結(jié)果表明,TA能顯著降低晚期支架再狹窄率和再狹窄程度,但機(jī)制不明確,從目前資料可證實(shí)TA抽出局部的有害物質(zhì)和減少血栓栓塞并發(fā)癥有顯著作用,但減輕炎癥與降低支架再狹窄是否有因果關(guān)系還需進(jìn)一步研究。
4TA技術(shù)聯(lián)合PPCI改善STEMI患者的預(yù)后
TA技術(shù)的應(yīng)用使STEMI患者即刻獲得良好的心肌再灌注,可明顯改善患者的預(yù)后。Kumbhani等[25]薈萃分析了2013年注冊(cè)的20個(gè)(11 321例)TA的臨床隨機(jī)對(duì)照研究資料,結(jié)果顯示MACE在血栓抽吸切除組減少(RR=0.81,P=0.006),全因死亡有下降趨勢(shì),但差異無(wú)統(tǒng)計(jì)學(xué)意義(RR=0.83,P=0.06)。雖然30 d的病死率沒(méi)有降低,但6~12個(gè)月的全因病死率降低36%,差異有統(tǒng)計(jì)學(xué)意義(P=0.016),6~12個(gè)月內(nèi)再梗死發(fā)生率降低了36%(P=0.017),支架內(nèi)血栓的發(fā)生率降低46% (P=0.021)及靶血管重建率也降低17%,體現(xiàn)了TA具有改善STEMI患者預(yù)后的價(jià)值。Sardella等[26]對(duì)STEMI患者采用TA后再行PPCI,隨訪24 個(gè)月發(fā)現(xiàn),MACE顯著降低(4.5%比13.7%,P=0.038)和心臟性死亡的發(fā)生率也明顯降低 (P=0.012)。手動(dòng)TA后再行支架置入術(shù)對(duì) STEMI患者改善心肌再灌注,并減少2年后心臟死亡和MACE。但近來(lái)Kilic等[27]研究認(rèn)為,TA與否對(duì)遠(yuǎn)期預(yù)后無(wú)明顯影響。當(dāng)然,TA尤其聯(lián)合冠狀動(dòng)脈內(nèi)注射血小板糖蛋白Ⅱb/Ⅲa受體拮抗劑改善患者預(yù)后的支持證據(jù)占多數(shù),由于選擇研究對(duì)象結(jié)構(gòu)不同,采用的抽吸裝置和方式不同,技術(shù)條件不同等因素可能會(huì)得到不同的結(jié)果。
5小結(jié)
總之,TA技術(shù)已經(jīng)發(fā)揮了較大的作用,降低血栓負(fù)荷,改善心肌灌注,降低血栓栓塞發(fā)生率和支架再狹窄率,改善臨床預(yù)后。雖然有些研究結(jié)果是中性的,但隨著TA技術(shù)的不斷成熟,抽吸經(jīng)驗(yàn)的不斷積累,抽吸裝置的不斷改進(jìn),尤其針對(duì)彎曲病變鈣化病變的抽栓系統(tǒng)的開(kāi)發(fā)利用以及其他的有效聯(lián)合措施,TA在STEMI的急診PPCI時(shí)的作用會(huì)越來(lái)越大。
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The Application Advances of Thrombus Aspiration in Acute Myocardial Infarction during Emergency Percutaneous Coronary InterventionTONGYu-tian1,WANGHuai-xin1,HUFeng-huan2. (1.DepartmentofCardiology,YiduCentralHospitalAffiliatedtoWeifangMedicalCollege,Weifang262500,China; 2.DepartmentofCardiology,FuwaiHospitalofCardiovascularDisease,Beijing100037,China)
Abstract:The no reflow or slow reflow following emergency percutaneous coronary intervention can affect clinical outcome and prognosis of the patients with acute myocardial infarction,the main mechanism of which is thrombus embolism.In theory,thrombus aspiration(TA) should be the effective approach. In recent years,the results of many clinical trials about TA have showed that it not only can make infarction-related artery(IRA)reopen,but also maintain microcirculatory patency of IRA,reduce the occurrences of no reflow or slow reflow.Recently,clinical studies proved that TA combined thrombolytic medicines and anti-platelet drugs with alternatives lessening thrombus burden can greatly improve reflow of IRA,decrease infarction size,inhibit myocardial remodeling,improve cardiac function,lower rates of recent and long-term major adverse cardiac events,reduce inflammation of lesion myocardium,decrease occurrences of in-stent restenosis and major bleeding complication,which consequently can improve the prognosis of acute myocardial infarction.
Key words:Acute myocardial infarction; Thrombus aspiration; Major adverse cardiac events; Percutaneous coronary intervention
收稿日期:2014-07-28修回日期:2015-03-21編輯:相丹峰
基金項(xiàng)目:濰坊市科學(xué)技術(shù)發(fā)展計(jì)劃(N201073)
doi:10.3969/j.issn.1006-2084.2015.18.027
中圖分類號(hào):R542.22
文獻(xiàn)標(biāo)識(shí)碼:A
文章編號(hào):1006-2084(2015)18-3336-04